ArticleCancer research2014
Neuregulin autocrine signaling promotes self-renewal of breast tumor-initiating cells by triggering HER2/HER3 activation.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- ADAM9 in tumor biology: molecular functions, clinical implications, and therapeutic targeting.Cellular & molecular biology letters · 2026Review
- COLEC12high tumor-associated macrophages orchestrate lenvatinib resistance and cancer stemness in hepatocellular carcinoma via paracrine NRG1-HER2/HER3 signaling.Clinical and molecular hepatology · 2026Article
- NRG1/ERBB3/ERBB2 Axis Triggers Anchorage-Independent Growth of Basal-like/Triple-Negative Breast Cancer Cells.Cancers · 2022Article
- Article
- Review
- Cancer Stem Cells-Key Players in Tumor Relapse.Cancers · 2021Review
- Canonical ErbB-2 isoform and ErbB-2 variant c located in the nucleus drive triple negative breast cancer growth.Oncogene · 2020Article
- Evaluation of the HER/PI3K/AKT Family Signaling Network as a Predictive Biomarker of Pathologic Complete Response for Patients With Breast Cancer Treated With Neratinib in the I-SPY 2 TRIAL.JCO precision oncology · 2018Article
- Genome-wide association and expression quantitative trait loci studies identify multiple susceptibility loci for thyroid cancer.Nature communications · 2017Article
- HER2 in Breast Cancer Stemness: A Negative Feedback Loop towards Trastuzumab Resistance.Cancers · 2017Review
- Development of a test that measures real-time HER2 signaling function in live breast cancer cell lines and primary cells.BMC cancer · 2017Article
- A functional signal profiling test for identifying a subset of HER2-negative breast cancers with abnormally amplified HER2 signaling activity.Oncotarget · 2016Article
- Heregulin/ErbB3 Signaling Enhances CXCR4-Driven Rac1 Activation and Breast Cancer Cell Motility via Hypoxia-Inducible Factor 1α.Molecular and cellular biology · 2016Article
- Article
- Yap1 promotes the survival and self-renewal of breast tumor initiating cells via inhibiting Smad3 signaling.Oncotarget · 2016Article
- RefSOFI for Mapping Nanoscale Organization of Protein-Protein Interactions in Living Cells.Cell reports · 2016Article
- Article
- Inhibition of Mouse Breast Tumor-Initiating Cells by Calcitriol and Dietary Vitamin D.Molecular cancer therapeutics · 2015Article
- Circulating Her-2/neu extracellular domain in breast cancer patients-correlation with prognosis and clinicopathological parameters including steroid receptor, Her-2/neu receptor coexpression.Pathology oncology research : POR · 2015Article
- Identifying and targeting tumor-initiating cells in the treatment of breast cancer.Endocrine-related cancer · 2015Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Currently, only patients with HER2-positive tumors are candidates for HER2-targeted therapies. However, recent clinical observations suggest that the survival of patients with HER2-low breast cancers, who lack HER2 amplification, may benefit from adjuvant therapy that targets HER2. In this study, we explored a mechanism through which these benefits may be obtained. Prompted by the hypothesis that HER2/HER3 signaling in breast tumor-initiating cells (TIC) promotes self-renewal and survival, we obtained evidence that neuregulin 1 (NRG1) produced by TICs promotes their proliferation and self-renewal in HER2-low tumors, including in triple-negative breast tumors. Pharmacologic inhibition of EGFR, HER2, or both receptors reduced breast TIC survival and self-renewal in vitro and in vivo and increased TIC sensitivity to ionizing radiation. Through a tissue microarray analysis, we found that NRG1 expression and associated HER2 activation occurred in a subset of HER2-low breast cancers. Our results offer an explanation for why HER2 inhibition blocks the growth of HER2-low breast tumors. Moreover, they argue that dual inhibition of EGFR and HER2 may offer a useful therapeutic strategy to target TICs in these tumors. In generating a mechanistic rationale to apply HER2-targeting therapies in patients with HER2-low tumors, this work shows why these therapies could benefit a considerably larger number of patients with breast cancer than they currently reach.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.